Host factors required for human polyomavirus replication and spread

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Polyomaviruses are ubiquitous viruses that infect virtually everyone on the planet. We currently know of thirteen different polyomaviruses that infect humans, which are mainly contracted during childhood. These viruses can persist within us for life and they can cause serious problems in immune-suppressed patients, including at least one type of cancer. One of the most significant medical problems that is caused by polyomavirus infection is in kidney transplantation, where a virus known as BK polyomavirus causes extensive damage to the kidneys and bladder. The only available drugs to treat infections with polyomaviruses are either ineffective or can damage the kidneys and so they are not viable options for use in kidney transplant patients, and as a consequence BK polyomavirus infection leads to an unacceptably high risk losing the transplanted kidney. Therefore, we have an urgent need to develop new therapeutics to combat the diseases caused by BK polyomavirus and related viruses. However, there is insufficient knowledge of the basic biology of these viruses.Polyomaviruses express only a handful of their own proteins and so they are particularly reliant on processes within our cells to successfully replicate and spread. We have recently developed large scale genetic screens to identify the genes in our cells that are crucial for BK polyomavirus infection. The proposed research will use state-of-the-art techniques to provide a detailed understanding of what factors within our cells BK polyomavirus needs. This knowledge will identify new ways that we can develop medicines to inhibit these viruses, which could have far reaching benefits for kidney transplant recipients and for treating other diseases caused by polyomaviruses.